Many natural polysaccharides, such as starch and alginate, are found in food or used as food ingredients. Starch is one of the most abundant polysaccharides occurring in nature. This biopolymer has a molecular formula of (C6H10O5)n, with n ranging from 300 to 1000 [1]. Starch is composed of a mixture of two polymers called amylose and amylopectin [1, 2]. Amylose molecules consists of α-D-glucopyranose units joined by α-1,4 acetal linkages. Amylopectin molecules are much larger and highly branched. The molecule contains α-1,4 linear bounds, and is branched through α-1,6 linkages [1, 2]. Most starches used in industry usually contain between 20 and 30% amylose with the remainder being amylopectin (70-80%) and minor components (less than 1%) such as lipids and protein [3].
Starch offers distinct advantages. Starch is relatively safe, having biocompatibility and biodegradability profiles well suited for in vivo applications. In the context of colloidal systems, starch has stabilizing properties making it a useful candidate for biomolecular development. Starch contains an abundance of hydroxyl groups capable of undergoing various chemical reactions characteristic of alcohols. This makes it possible for a variety of drugs, targeting moieties, metal chelators, fluorescence probes, etc. to be conjugated to starch-based materials. Starch-based materials can also be quite cost effective. Despite these advantages, starch has had limited use as a biomaterial and in drug delivery applications. Native starch has limited use due to its poor mechanical and chemical properties; however, various modifications can be made to improve the properties of starch and broaden its applications. The most common chemical modifications are grafting, oxidation, esterification, etherification, and hydrolysis. The grafting of starch with acrylic-based monomers can produce materials with potential drug delivery and biomedical applications due to the combination of biodegradable and stabilizing properties of starch with pH-responsive characteristics of acrylic polymer.
Starch-xanthan gum hydrogels have been synthesized for controlled drug delivery by cross-linking starch and xanthan gum by sodium trimethaphosphate [4]. Starch has been modified by grafting polymerization of various vinyl monomers [5] using radiation, photolysis, or catalysts and initiators such as metallic ions, peroxides, or persulfate [5-12]. Grafting of vinyl monomers onto starch is generally achieved by free radical initiation. Starch graft copolymers have been used as hydrogels, flocculants, ion exchangers, superabsorbents, and so on [13-18].
Hydrophilic acrylic monomers can form hydrogels with adjustable swelling kinetics and have been utilized for drug delivery and other biomedical applications such as improvement of osteoblast adhesion [19-21]. Combination of biodegradable properties of starch with pH responsive characteristics of acrylic based polymers may lead to interesting hydrogels with potentials in biomedical and drug delivery. Previously published work has shown that potassium persulfate is able to initiate grafting of methacrylic acid onto starch; however, substantial amount of homopolymer is formed [22]. By using potassium persulfate/sodium thiosulfate redox initiation system, Hebeish et al. were able to efficiently graft polymethacrylic acid onto starch while minimizing homopolymer formation [6, 7].
In many applications, fast phase transition in response to environmental stimuli, such as pH, is desirable. However, bulk hydrogels of large dimensions normally undergo slow dimensional change because conformational changes in polymeric networks and diffusion of solute and water through the network take time. Since the response time is proportional to the square of diffusion distance, the phase transition rate can be controlled by adjusting hydrogel dimensions [23]. Generally, nano-sized polymers undergo swelling equilibrium, and phase transition in order of micro-seconds. Hence, stimulus responsive nanoparticles can be potentially useful in stimulus-responsive drug delivery, and can serve as sensors or microswitches because of their extremely fast response to stimuli.
Despite numerous publications on grafting polymerization of vinyl monomers, the published data on development and characterization of nano-sized starch based pH sensitive particles is very limited. Saboktakin et al. have recently described the grafting of the polymethacrylic acid onto carboxymethyl starch to produce bulk polymer [24]. The authors have subsequently used a freeze drying method to produce nanopowders; however, their method does not produce stable colloidal dispersion of nanoparticles in aqueous medium. Saboktakin et al. have also described the grafting of the polymethacrylic acid onto chitosan nanoparticles as delivery systems for paclitaxel [24(a)]. Hirosue et al. have described in international patent publication WO 2010/084060 a polymer having a starch backbone onto which methylacrylate monomer was grafted by atom transfer radical polymerization (ATRP) subsequent to modification of backbone hydroxyl groups by a linker such as 2-bromo isobutyryl bromide. Nanoparticles were formulated with the starch polymer by an emulsion diffusion method.